Abstract
BackgroundExercise intolerance in systemic sclerosis (SSc) is typically attributed to cardiopulmonary limitations. However, problems with skeletal muscle oxygen extraction have not been fully investigated. This study used cardiovascular magnetic resonance (CMR)-augmented cardiopulmonary exercise testing (CMR-CPET) to simultaneously measure oxygen consumption and cardiac output. This allowed calculation of arteriovenous oxygen content gradient, a recognized marker of oxygen extraction. We performed CMR-CPET in 4 groups: systemic sclerosis (SSc); systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH); non-connective tissue disease pulmonary hypertension (NC-PAH); and healthy controls.MethodsWe performed CMR-CPET in 60 subjects (15 in each group) using a supine ergometer following a ramped exercise protocol until exhaustion. Values for oxygen consumption, cardiac output and oxygen content gradient, as well as ventricular volumes, were obtained at rest and peak-exercise for all subjects. In addition, T1 and T2 maps were acquired at rest, and the most recent clinical measures (hemoglobin, lung function, 6-min walk, cardiac and catheterization) were collected.ResultsAll patient groups had reduced peak oxygen consumption compared to healthy controls (p < 0.022). The SSc and SSc-PAH groups had reduced peak oxygen content gradient compared to healthy controls (p < 0.03). Conversely, the SSc-PAH and NC-PH patients had reduced peak cardiac output compared to healthy controls and SSc patients (p < 0.006). Higher hemoglobin was associated with higher peak oxygen content gradient (p = 0.025) and higher myocardial T1 was associated with lower peak stroke volume (p = 0.011).ConclusionsReduced peak oxygen consumption in SSc patients is predominantly driven by reduced oxygen content gradient and in SSc-PAH patients this was amplified by reduced peak cardiac output.Trial registration The study is registered with ClinicalTrials.gov Protocol Registration and Results System (ClinicalTrials.gov ID: 100358).
Highlights
Exercise intolerance in systemic sclerosis (SSc) is typically attributed to cardiopulmonary limitations
Demographics and clinical data There were no significant differences in age, sex, height, weight or body surface area (BSA) between the groups (Table 1)
In both the SSc and SSc-pulmonary artery hypertension (PAH) groups, 14 patients (93%) had limited cutaneous systemic sclerosis, while the remaining patient had a diagnosis of diffuse cutaneous systemic sclerosis (Auto-antibody specificities detailed in Additional file 1: Table S1)
Summary
Exercise intolerance in systemic sclerosis (SSc) is typically attributed to cardiopulmonary limitations. This study used cardiovascular magnetic resonance (CMR)-augmented cardiopulmonary exercise testing (CMR-CPET) to simultaneously measure oxygen consumption and cardiac output. This allowed calculation of arteriovenous oxygen content gradient, a recognized marker of oxygen extraction. It has been shown that SSc patients have skeletal muscle inflammation, fibrosis and vasculopathy [1], all of which can reduce tissue oxygen extraction. Understanding the relative importance of these factors is vital for targeting therapy This is difficult with conventional cardiopulmonary exercise testing (CPET) as only oxygen consumption (VO2) is directly measured. Our method (CMR-CPET) provides quantitative assessment of exercise capacity through combined direct measurement of both VO2 and cardiac output. T1 and T2 mapping can be performed in order to assess myocardial fibrosis and inflammation, which may be pertinent in SSc patients
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